The primary goal of this R01 application is to investigate whether a psychotherapeutic approach, group Cognitive Behavioral Therapy (CBT) plus relapse prevention program Therapeutic Interactive Voice Response (TIVR), modifies the dysfunctional sensory, emotional, and cognitive neural circuitry associated with chronic pain as examined by functional magnetic resonance imaging (fMRI). We propose to apply previously tested and accepted paradigms for symptom provocation (acute pain, emotional stimuli and cognitive tasks) to investigate psychological effects on neural correlates of chronic pain. Because chronic pain is not just an isolated sensory event but rather a complex sensory, cognitive and emotional experience, it is reasonable to expect that an intervention which improves chronic pain such as coping skills training followed by the relapse prevention program will alter responses to provocative stimuli and thus the underlying neural circuitry. Our pilot study (R21NIDA) demonstrated that patients with chronic musculoskeletal pain not only benefit from group CBT but continue to improve with the use of our telephone based relapse prevention program (TIVR). In addition, our fMRI pilot study results reveal that after group CBT chronic pain patients show reduced insula (IC), amygdala and primary somatosensory cortex (S1) reactivity to arousing stimuli, and increased activation in the prefrontal cortex and anterior cingulate cortex (ACC). This suggests that CBT may increase cortical suppression of amygdala and S1 and thus may be related to the reduction and the experience of pain. In this application we take advantage of the unique opportunity to obtain longitudinal clinical and neuroimaging data. One hundred twenty subjects who meet inclusion and exclusion criteria for the fMRI study will be randomly assigned to two study conditions: Eighty to 11-week CBT Treatment Condition and forty to Attention Control Condition. Eighty subjects who undergo group CBT will be randomized to TIVR or Treatment-as-Usual. Participants will undergo three fMRI examinations (at baseline, after group and after TIVR interventions) to explore two study goals: 1) whether psychological treatment changes the function of brain neural circuitry in response to application of acute noxious stimuli, cognitive tasks and emotional stimuli; 2) whether there is a relationship between altered activation in brain areas associated with the attentional, affective, and sensory aspects of chronic pain and quantifiable improvement in clinical measures reported at the conclusion of group CBT and 4 months of TIVR. Our approach is novel as there are no published studies that explore the neurobiological effects of psychotherapeutic approaches in chronic pain. Through the joint examination of painful, emotional, and cognitive paradigms via brain imaging and implementing this approach in a longitudinal, clinical framework, we will open important and novel avenues of research on chronic pain. PUBLIC HEALTH RELEVANCE: This proposed study will test the hypothesis that CBT plus relapse prevention Therapeutic Interactive Voice Response (TIVR) program modifies the dysfunctional sensory, emotional, and cognitive neural circuitry associated with chronic pain as examined by functional magnetic resonance imaging (fMRI). As we continue to discover that pain experience is strongly modulated by interactions of ascending and descending pathways, better understanding these modulatory mechanisms is of great importance for developing and appropriately applying effective treatment. We believe that our study will significantly contribute to this.